188 research outputs found

    Attitudes Toward International Harmonization Efforts: A Cross-Cultural Study.

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    The last two decades have seen a significant increase in the number and size of multinational corporations and a growing global investment environment. Linked to that growth has been a call for standards that produce accounting information that is capable of crossing national boundaries. One of the groups of professional elites that have addressed the call for harmonized international accounting standards is the International Accounting Standards Committee (IASC). The IASC objective (IASC 1988, 1) states that it will work generally for the improvement and harmonization of regulations, accounting standards and procedures ... To address such a goal, the IASC has had to deal with a number of ethnocentric elements, which are generally considered to act as potential barriers to the harmonization process. Culture is a common referent in the literature as one of these potential barriers. This research investigates the link between culture and attitudes toward the harmonization efforts of the IASC. The concept of culture was defined using the four work-environment cultural dimensions developed by Hofstede (1980). The attitudes toward harmonization efforts was operationalized by responding to general and specific statements related to the IASC Comparability Project--Exposure Draft 32. Accounting professionals working in the overseas offices of Big Six accounting firms were used to examine the culture/international harmonization link. The results of the t-tests indicate partial support for the link between Hofstede\u27s cultural dimensions and both general and specific attitudes toward the IASC\u27s Comparability Project. Two of the four cultural dimensions (i.e., uncertainty avoidance and individualism) offer a stronger conceptual link concerning the general topic of harmonization attitudes. The results tended to verify this conceptual tie. An additional analysis using logistic and profit regression lends additional support for Hofstede\u27s contention that the dimensions are measures of group values (i.e., national culture) rather than individual values

    Polycistronic Delivery of IL-10 and NT-3 Promotes Oligodendrocyte Myelination and Functional Recovery in a Mouse Spinal Cord Injury Model.

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    One million estimated cases of spinal cord injury (SCI) have been reported in the United States and repairing an injury has constituted a difficult clinical challenge. The complex, dynamic, inhibitory microenvironment postinjury, which is characterized by proinflammatory signaling from invading leukocytes and lack of sufficient factors that promote axonal survival and elongation, limits regeneration. Herein, we investigated the delivery of polycistronic vectors, which have the potential to coexpress factors that target distinct barriers to regeneration, from a multiple channel poly(lactide-co-glycolide) (PLG) bridge to enhance spinal cord regeneration. In this study, we investigated polycistronic delivery of IL-10 that targets proinflammatory signaling, and NT-3 that targets axonal survival and elongation. A significant increase was observed in the density of regenerative macrophages for IL-10+NT-3 condition relative to conditions without IL-10. Furthermore, combined delivery of IL-10+NT-3 produced a significant increase of axonal density and notably myelinated axons compared with all other conditions. A significant increase in functional recovery was observed for IL-10+NT-3 delivery at 12 weeks postinjury that was positively correlated to oligodendrocyte myelinated axon density, suggesting oligodendrocyte-mediated myelination as an important target to improve functional recovery. These results further support the use of multiple channel PLG bridges as a growth supportive substrate and platform to deliver bioactive agents to modulate the SCI microenvironment and promote regeneration and functional recovery. Impact statement Spinal cord injury (SCI) results in a complex microenvironment that contains multiple barriers to regeneration and functional recovery. Multiple factors are necessary to address these barriers to regeneration, and polycistronic lentiviral gene therapy represents a strategy to locally express multiple factors simultaneously. A bicistronic vector encoding IL-10 and NT-3 was delivered from a poly(lactide-co-glycolide) bridge, which provides structural support that guides regeneration, resulting in increased axonal growth, myelination, and subsequent functional recovery. These results demonstrate the opportunity of targeting multiple barriers to SCI regeneration for additive effects

    PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination.

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    Spinal cord injury (SCI) is a devastating condition that may cause permanent functional loss below the level of injury, including paralysis and loss of bladder, bowel, and sexual function. Patients are rarely treated immediately, and this delay is associated with tissue loss and scar formation that can make regeneration at chronic time points more challenging. Herein, we investigated regeneration using a poly(lactide-co-glycolide) multichannel bridge implanted into a chronic SCI following surgical resection of necrotic tissue. We characterized the dynamic injury response and noted that scar formation decreased at 4 and 8 weeks postinjury (wpi), yet macrophage infiltration increased between 4 and 8 wpi. Subsequently, the scar tissue was resected and bridges were implanted at 4 and 8 wpi. We observed robust axon growth into the bridge and remyelination at 6 months after initial injury. Axon densities were increased for 8 week bridge implantation relative to 4 week bridge implantation, whereas greater myelination, particularly by Schwann cells, was observed with 4 week bridge implantation. The process of bridge implantation did not significantly decrease the postinjury function. Collectively, this chronic model follows the pathophysiology of human SCI, and bridge implantation allows for clear demarcation of the regenerated tissue. These data demonstrate that bridge implantation into chronic SCI supports regeneration and provides a platform to investigate strategies to buttress and expand regeneration of neural tissue at chronic time points

    Combinatorial lentiviral gene delivery of pro‐oligodendrogenic factors for improving myelination of regenerating axons after spinal cord injury

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    Spinal cord injury (SCI) results in paralysis below the injury and strategies are being developed that support axonal regrowth, yet recovery lags, in part, because many axons are not remyelinated. Herein, we investigated strategies to increase myelination of regenerating axons by overexpression of platelet‐derived growth factor (PDGF)‐AA and noggin either alone or in combination in a mouse SCI model. Noggin and PDGF‐AA have been identified as factors that enhance recruitment and differentiation of endogenous progenitors to promote myelination. Lentivirus encoding for these factors was delivered from a multichannel bridge, which we have previously shown creates a permissive environment and supports robust axonal growth through channels. The combination of noggin+PDGF enhanced total myelination of regenerating axons relative to either factor alone, and importantly, enhanced functional recovery relative to the control condition. The increase in myelination was consistent with an increase in oligodendrocyte‐derived myelin, which was also associated with a greater density of cells of an oligodendroglial lineage relative to each factor individually and control conditions. These results suggest enhanced myelination of regenerating axons by noggin+PDGF that act on oligodendrocyte‐lineage cells post‐SCI, which ultimately led to improved functional outcomes.Spinal cord injury (SCI) results in paralysis below the injury and strategies are being developed that support axonal regrowth, yet recovery lags, in part because many axons are not remyelinated. Herein, we investigated strategies to increase myelination of regenerating axons by overexpression of platelet‐derived growth factor‐AA and noggin either alone or in combination in a mouse SCI model.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146575/1/bit26838_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146575/2/bit26838.pd

    The importance of 1,5-oxygen-chalcogen interactions in enantioselective isochalcogenourea catalysis

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    Syngenta (Case Award to DJP) and a Philip Leverhulme Prize for funding (SLC, AE). RKM and PHW are grateful to the American Chemical Society Petroleum Research Fund and National Science Foundation (NSF-MRI: CHE-1429616).The importance of 1,5-O···chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch = O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O···Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density Functional Theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.PostprintPeer reviewe

    Systematic review of exercise and the long-term outcomes of the treatment for obesity.

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    We systematically reviewed randomised controlled trials (RCTs) of obesity treatments in adults and assessed long term effects on weight and risk factors for disease

    Isothiourea-catalyzed enantioselective addition of 4-nitrophenyl esters to iminium ions

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    The authors thank AstraZeneca and the EPSRC (grant codes EP/M506631/1; J.N.A. and EP/J018139/1; A.B.F.) for funding. The European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC Grant Agreement No. 279850 is also acknowledged. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.Isothioureas catalyze the enantioselective addition of 4-nitrophenyl esters to tetrahydroisoquinoline-derived iminium ions. 4-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the 4-nitrophenyl ester, is used to facilitate catalyst turnover in this reaction process. Optimization showed that 4-nitrophenyl esters give the best reactivity in this protocol over a range of alternative aryl esters, with the observed enantioselectivity markedly dependent upon the nature of the iminium counteri-on. Highest yields and enantioselectivity were obtained using iminium bromide ions generated in situ via photoredox catalysis using BrCCl3 and Ru(bpy)3Cl2 (0.5 mol%) and commercially available tetramisole (5 mol%) as the Lewis base catalyst. The scope and limitations of this procedure was developed, giving the desired β-amino amide products in up to 96% yield, 79:21 dr and ermajor (2R,1′S) 99.5:0.5.PostprintPeer reviewe

    Feasibility of an implementation intervention to increase attendance at diabetic retinopathy screening: protocol for a cluster randomised pilot trial

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    Background: Diabetic retinopathy screening (DRS) leads to the earlier detection of retinopathy and treatment that can prevent or delay the development of diabetes-related blindness. However, uptake continues to be sub-optimal in many countries, including Ireland. Routine management of type 2 diabetes largely takes place in primary care. As such, there may be an opportunity in primary care to introduce interventions to improve DRS uptake. However, few studies test the feasibility of interventions to enhance DRS uptake in this context. Our aim is to investigate the feasibility of an implementation intervention (IDEAs (Improving Diabetes Eye screening Attendance)) delivered in general practice to improve the uptake of the national DRS programme, RetinaScreen. Methods: The IDEAs study is a cluster randomised pilot trial with an embedded process evaluation and economic evaluation. Following stratification by practice size, eight general practices (clusters) will be randomly allocated to intervention (n = 4) or wait-list control groups (n = 4). The intervention will be delivered for 6 months, after which, it will be administered to wait-list control practices. The intervention is multi-faceted and comprises provider-level components (training, audit and feedback, health care professional prompt, reimbursement) and patient-level components (GP-endorsed reminder with information leaflet delivered opportunistically face-to-face, and systematically by phone and letter). Patient inclusion criteria are type 1 or type 2 diabetes and DRS programme non-attendance. A multi-method approach will be used to determine screening uptake, evaluate the trial and study procedures and examine the acceptability and feasibility of the intervention from staff and patient perspectives. Quantitative and qualitative data will be collected on intervention uptake and delivery, research processes and outcomes. Data will be collected at the practice, health professional and patient level. A partial economic evaluation will be conducted to estimate the cost of delivering the implementation intervention in general practice. Formal continuation criteria will be used to determine whether IDEAs should progress to a definitive trial. Discussion: Findings will determine whether IDEAsis feasible and acceptable and will be used to refine the intervention and study procedures. A definitive trial will determine whether IDEAs is a cost-effective intervention to improve DRS uptake and reduce diabetes-related blindness. Trial registration: ClinicalTrials.gov NCT03901898. Registered 3rd April 2019

    A proposed unified framework to describe the management of biological invasions

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    Acknowledgements This paper arose from a workshop of the Invasion Dynamics Network (InDyNet) in Berlin in 2018, funded by the Deutsche Forschungsgemeinschaft (DFG) Grant JE 288/8-1, which included a Mercator Fellowship for DLS. Additional support was received through DFG Grants JE 288/9- 1 and JE 288/9-2 to JMJ, the G.E. Hutchinson Chair to DLS and the project ‘‘Capacity Building Neobiota’’ (Austrian Federal Ministry for Sustainability and Tourism) to WR. AN, PP and JP were supported by long-term research development project no. RVO 67985939, project 17-19025S and EXPRO grant 19-28807X (Czech Science Foundation). IJ was supported by the J. E. Purkyneˇ Fellowship of the Czech Academy of Sciences. We also thank the referees for this paper for their critical and constructive comments.Peer reviewedPublisher PD
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